Understanding the mechanism of action of HDACs Inhibitors to improve Childhood Leukemia treatments

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Hugo Wurtele, PhD

Hugo Wurtele is assistant professor in the department of medicine of the Université de Montréal, and his research activities are conducted at the Maisonneuve-Rosemont Hospital research center in Montreal. After completing a PhD in molecular biology at the Université de Montréal in Dr Pierre Chartrand’s laboratory, Dr Wurtele performed his post-doctoral fellowships in Dr Alain Verreault’s lab at the Institute for immunology and cancer (IRIC) in Montreal, and in Dr Jef Boeke’s lab at the High Throughput Biology Center of the Johns Hopkins University in Baltimore, USA. He established his research group in august 2011 and has since been awarded a Fonds de la recherché en santé (FRSQ) Chercheurs-boursiers Junior 1 award in 2012. His laboratory is now funded through grants from the Cole Foundation, the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Council (NSERC). Dr Wurtele’s work is focused on the interplay between chromatin structure and the cellular response to cancer chemotherapy drugs.

Funds provided by the Cole Foundation will be used to investigate the mechanism of action of a novel therapeutic protocol, which combines chemotherapy drugs already used in the clinic and “Histone Deacetylase Inhibitors” (HDACi). Indeed, the therapeutically-relevant cellular targets of HDACi remain unclear, which renders the rational design of such improved treatment regimen more challenging. Moreover HDACi affect numerous cellular pathways, in addition to ones relevant to cancer, leading to “off-target” effects. Mitigating this problem is especially important in childhood cancers, since long-term consequences of such side effects are difficult to predict. To attain this goal, experiments will be performed using the powerful yeast model system as a first step toward unraveling the mechanism of action of HDACi in human leukemia. Yeast will be used to understand the effect of HDACi on various proteins that are important to deal with the genetic damage caused by chemotherapy drugs. These proteins are envisioned as potential targets for the development of new drugs to improve chemotherapy regimen used in the treatment of pediatric leukemia, and to diminish unwanted side effects associated with the use of HDACi. A better understanding of the mechanism through which HDACi affect cancer cells will thus ultimately allow clinicians to fully exploit the potential of these new drugs.